Six different types of cancer (i.e., breast, lung, colorectal, esophageal, gastric, and thyroid cancer) have high rates of incidence or mortality worldwide. It has been shown that activation of de novo lipogenesis is an early and common event in the cancer microenvironment. In this study, we performed lipid imaging and profiling for 134 tissue samples from six different types of cancer using matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry, with 2,5-dihydroxybenzoic acid and 1,8-bis(dimethyl-amino)naphthalene as matrices in the positive and negative ion modes, respectively. Multivariate statistical analysis coupled with lipid distribution images revealed that significantly increased levels of monounsaturated fatty acids and monounsaturated phosphatidylcholines relative to polyunsaturated fatty acids and polyunsaturated phosphatidylcholines were observed in the cancer microenvironment compared with the adjacent normal tissue. The immunohistochemical assay indicated that fatty acid synthase, stearoyl-CoA desaturase-1, and choline kinase α were up-regulated in the cancer microenvironment compared with the adjacent normal tissue. Our findings suggest that de novo lipogenesis was activated in six types of cancer to promote a biosynthesis of lipids with monounsaturated acyl chains and to suppress a biosynthesis of polyunsaturated lipids in the cancer microenvironment.

Abstract-Cardiac myosin binding protein-C (cMyBPC) is a modular protein consisting of 11 domains whose precise function and sarcomeric arrangement are incompletely understood. Identification of hypertrophic cardiomyopathy (HCM)-causing missense mutations in cMyBPC has highlighted the significance of certain domains. Of particular interest is domain C5, an immunoglobulin-like domain with a cardiac-specific insert, which is of unknown function yet is the site of two HCM-causing missense mutations. To identify interactors with this region, a human cardiac cDNA library was screened in a yeast two-hybrid (Y2H) assay using the C5 sequence as bait. Screening Ͼ7ϫ10 6 clones surprisingly revealed that domain C5 preferentially bound to clones encoding C-terminal fragments of cMyBPC; the interacting region was narrowed to domain C8 by deletion mapping. A surface plasmon resonance assay using purified recombinant cMyBPC domains was used to measure the affinity of C5 and C8 in vitro (K a ϭ1ϫ10 5 mol/L Ϫ1 ). This affinity was decreased about 2-fold by the HCM mutation R654H, and by at least 10-fold by the mutation N755K. Further Y2H assays also demonstrated specific binding between domains C7 and C10 of cMyBPC. Based on these novel interactions, and previous biochemical and structural data, we propose that cMyBPC molecules trimerize into a collar around the thick filament, with overlaps of domains C5-C7 of one cMyBPC with C8-C10 of another. We speculate that this interaction may be dynamically formed and released, thereby restricting or favoring cross-bridge formation, respectively. We suggest that the HCM mutations act by altering the cMyBPC collar, indicating its importance in thick filament structure and regulation.

Water pollution by heavy metal ions is currently of great concern due to their high toxicity and carcinogenicity. In recent years, great efforts have been devoted to the search for new cost-effective adsorbents derived from biomass. Lignin is a natural amorphous polymer that has great potential for use as a building block in the production of biorenewable materials. Due to its unique polyphenol structure, physicochemical properties, and abundance, a wide variety of sorbents, particularly heavy metal ion sorbents, can be potentially obtained from lignin. This paper provides a comprehensive review of the literature about different feedstock lignin and versatile lignin derivatives used as heavy metal ion adsorbents. The adsorption capability improvement mechanism of the lignin derivatives and the comparison with commercial resins are also discussed. Therefore, this review aims to discuss the different modification categories that have been reported for the conversion of lignins into advanced heavy metal ion adsorbents. Most importantly, adsorbents derived from lignin can confer high environmental benefits due to its stability, biocompatibility and abundance in the plant kingdom. This review may pave the way for the design and fabrication of new lignin-based adsorbents with enhanced adsorbent performance for heavy metal ions in water.

No abstract

No abstract

Our study revealed that the consideration of CRC stages would be necessary in diagnostic biomarker discovery, as well as that attention should be paid to the facile loss of methyl chloride from the [M + Cl](-) form of LPC(16:0) in its tandem mass spectrum.

Lignin-based dithiocarbamate (LDTC) was synthesized by anchoring the chelating agent of dithiocarbamate to the ortho sites of phenol hydroxyl groups in the alkaline lignin matrix. The LDTC biomaterial was characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and elemental analysis. Due to the cross-linked polymer matrix, high content of dithiocarbamate groups and excellent complex ability, the LDTC was used as a new bio-adsorbent for the removal of metallic ions from aqueous solution. The influences of pH, LDTC dosage, contact time, and initial metallic ion concentration on adsorption capacity and competitive adsorption of multi metallic ions have been investigated. The regeneration of LDTC was also studied. The results demonstrated that LDTC showed fast adsorption, higher adsorption capacity and feasible regeneration compared to other lignin-based bio-adsorbents even activated carbon. The adsorption kinetics and adsorption isotherms were fitted well by a pseudo second-order model and D-R model, respectively. Moreover, the resultant metal-loaded solid bio-sorbents (LDTC-M) were firstly estimated as free radical scavengers due to the inherent merits of naturally occurring polyphenols which therefore could provide a potential way for value-added usage of the LDTC-M.

The stress of nebulization has been shown to alter the properties of liposomal drugs. What has not been demonstrated is whether nebulized liposomes differ as a function of droplet size. Because droplet size influences lung deposition, liposomes with different properties could be deposited in different areas of the lung (e.g., central vs. peripheral). In this report, a liposomal amikacin formulation (Arikace, a registered trademark of Transave, Inc., Monmouth Junction, NJ) that is being developed as an inhaled treatment for gram negative infections was aerosolized with an eFlow (registered trademark of PARI, GmbH, Munich, Germany) nebulizer, reclaimed from the various stages of an Andersen cascade impactor (ACI) and analyzed for lipid-to-drug (L/D) (w/w) ratio, amikacin retention, and liposome size. For the nebulized solution, 99.7% of the total deposited drug was found on ACI stages 0 through 5, which have cutoff diameters of 9, 5.8, 4.7, 3.3, 2.1, and 1.1 microm, respectively. Properties were found to differ for drug reclaimed on stage 0 compared stages 1-5, which were not different from one another. For drug found on stages 1-5 (97% of total drug), the averages (n = 3) for L/D, percent encapsulated amikacin, and liposome mean diameter ranged from 0.59 to 0.68 (w/w), 71% to 75%, 248 to 282 nm, respectively. Drug found on stage 0 (2.8% of total drug) had an average L/D ratio of 0.51 and average liposome mean diameter of 375 nm. Examination of another batch of liposomal amikacin revealed no statistically significant differences between drug reclaimed on stages 0-5. Although a droplet size dependence was noted for one batch of Arikace aerosolized with the eFlow, the effect was considered to be inconsequential because the fraction in doubt represented nonrespirable particles >9 microm and accounted for <3% of the total deposited dose. The methodology applied here appears useful in evaluating aerosolized liposome systems. However, our results should not be assumed to apply to other liposome/drug compositions and nebulizers.